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Palbociclib Plus Fulvestrant in Advanced Breast Cancer: Overall Survival Analysis of PALOMA-3

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Key Points

  • The improvement in overall survival in the palbociclib plus fulvestrant group was not statistically significant in the total trial population.
  • A significant survival benefit with palbociclib plus fulvestrant was observed in the 79% of study patients with sensitivity to previous endocrine therapy. 

An overall survival analysis of the PALOMA-3 trial reported by Turner et al in The New England Journal of Medicine found that the addition of the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor palbociclib (Ibrance) to fulvestrant (Faslodex) improved survival among patients with hormone receptor–positive, HER2-negative advanced breast cancer who had sensitivity to previous endocrine therapy, with the improvement not being significant in the entire study population.

The previously reported primary analysis of the trial showed a significant improvement in progression-free survival with the addition of palbociclib to fulvestrant among all patients, supporting the 2017 approval of palbociclib and fulvestrant in patients with disease progression following endocrine therapy.

Study Details 

In the double-blind phase III trial, 521 patients with hormone receptor–positive, HER2-negative advanced breast cancer who had progression or relapse during previous endocrine therapy were randomly assigned 2:1 to receive palbociclib plus fulvestrant (n = 347) or placebo plus fulvestrant (n = 174). Palbociclib was given orally at 125 mg once daily for 21 consecutive days followed by 7 days off in 28-day cycles. Fulvestrant was given intramuscularly at 500 mg every 14 days for the first three injections and then every 28 days. The current analysis is a prespecified analysis of overall survival. 

Overall Survival

Median follow up was 44.8 months. Among all patients, median overall survival was 34.9 months in the palbociclib plus fulvestrant group vs 28.0 months in the placebo plus fulvestrant group (hazard ratio [HR] = 0.81, P = .09). Among the 410 patients (79% of study population) with sensitivity to previous endocrine therapy, median overall survival was 39.7 months in the palbociclib plus fulvestrant group vs 29.7 months in the placebo plus fulvestrant group (HR = 0.72; 95% confidence interval [CI] = 0.55–0.94). Among 111 patients without documented sensitivity to previous endocrine therapy, median overall survival was 20.2 months vs 26.2 months (HR = 1.14, 95% CI = 0.71–1.84).

 A total of 16% of patients in the placebo plus fulvestrant group and 4% in the palbociclib plus fulvestrant group received CDK4/6 inhibitor treatment after completion of study treatment. The median duration of subsequent anticancer therapy was similar in the two groups. The median time to receipt of chemotherapy was 17.6 months in the palbociclib plus fulvestrant group vs 8.8 months in the placebo plus fulvestrant group (HR = 0.58, P < .001). The investigators noted that no new safety signals were observed during the 44.8 months of follow-up.

The investigators concluded, “Among patients with hormone receptor–positive, HER2-negative advanced breast cancer who had sensitivity to previous endocrine therapy, treatment with palbociclib [plus] fulvestrant resulted in longer overall survival than treatment with placebo [plus] fulvestrant. The differences in overall survival in the entire trial group were not significant.”

Disclosure: The study was funded by Pfizer. The study authors’ full disclosures can be found at nejm.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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